N-thiotrichloromethyl amides and parasiticidal compositions containing them



Patented May 22, 1951 UNITED STATES PATENT OFFICE N-THIOTRICHLOROMETHYL AMIDES AND PARASITICIDAL COMPOSITIONS CON-- TAINING THEM Roger S. Hawley, Linden, Allen R. Kittleson, Cranford, and Paul V. Smith, Jr., Westfield, N. 3., assignors to Standard Oil Development Company, a corporation of Delaware No Drawing. Application June 21, 1949, Serial No. 100,542

16 Claims. (Cl. 16722) 1 2 This invention relates to new and useful imin which R represents an organic residue or an provements in parasiticidal preparations and organic radical which is linked to the X group by more particularly to improved fungicides, insectia carbon atom, X is part of an acylgroup such as cides and germicides. This invention also relates for example to methods of protecting organic material subject 5 to attack by W orders of organisms. This invention further relates to the synthesis of new 2 chemical compounds, N-thictrichloromethyl amides. 0

U. S. applications Serial No. 773,925, filed Sep- 10 tember 13, 1947, and Serial No. 90,271, filed April 28, 1949, disclose N-thiotrichloromethyl imides of and dicarboxylic acids as active parasiticides. v x

It has now been found that a large number of organic compounds containing the NSCC13 15 linked to one acyl group are extremely effective for checking the growth of bacteria, fungi, and insects. These new compounds may thus be used as novel ingredients of seed and plant protectants represents and olfgamc esldue, an Organ! because of their disinfecting action on soil conradlcafl. hydrogen radlcal- When Rand are taining harmful organisms. organic radlcals, they m P the Same differ- The physiologically active compounds of this ent and also be 9 aromatic, yc c. invention may thus best be represented as haw heterocycllc, and their substituted derivatives. ing the NSCC13 group in which the nitrogen is when and are organic residues! they are linked to one acyl group. The phrase acyl group usually dlfielfent 1n 1 and are lmked orefers to groups of the following character fl formmg cychc The Orgamc residue may contam a etc. (see Hackh, Chemical Dictionary, Second Edition, page 21). The compounds of this inveno p W ch is l ed to the N atom. This is not tion may thus be considered broadly as amides, an acyl type linkage, however, as the i. e., N-thiotrichloromethyl amides, and more specifically as substituted amides and sulfonamides. Suitable amide compounds of the indicated type are thus illustrated in Formula I: 40

group of the R organic residue is linked to neither a carbon atom or a hydrogen atom as described above. Characteristically these compounds are substituted secondary amides of monobasic acids.

Formula I 3 Suitable amide type compounds are thus illustrated more particularly below:

cal

N S 0 01: t

l-acetyl-3-thiotrlchloromethyl-5,5-dimethylhydantoin Nthiotrichlorometliyl-N-butylbenzenesulfonamide The novel N-thiotrichloromethyl amide compounds of this invention may be prepared in general by the reaction of perchloromethyl mercaptan (ClSCCls), with the corresponding amide or the metal salt of this compound. Formula II illustrates this reaction between phenyl benzene sulfonamide and perchloromethyl mercaptan, where M represents hydrogen or a metal.

0 S NM 0180013 0 S NSOCh MCl Formula II The preparation of the amide starting materials and their metal salts is well known in the art and is not the subject of this invention, and therefore has not been here described.

When the amide salt is used as a starting material for the production of N-thiotrichloromethyl amide derivatives of this invention, the salt is first dispersed in an organic liquid such as benzene or dioxane and while stirring and heating to about 50-80 C., an approximately equal molecular quantity of perchloromethylmercaptanis added over a period of about 1 to 2 hours. The reaction is continued for about 3 to 4 hours after all the mercaptan has been added. After cooling, the reaction mixture is filtered to remove the metal halide and any unreacted amide salt and in some cases, a portion of the N-thiotrichloromethyl amide. The remainder of the N-thiotrichloromethyl amide is recovered by concentrating the solvent filtrate and recrystallizing the residue from a suitable solvent. Any N-thiotrichloromethyl amide in the original filter cake may be recovered by washing with water to remove the metal halide and um'eacted amide salt. The water-insoluble product may then be further purified by recrystallization from a suitable solvent.

The compounds of this invention can also be prepared by the general method of dissolving the desired amide, without first forming the metal salt, in aqueous alkaline solution, followed by addition of about an equal molecular quantity of perchloromethyl mercaptan. The mixture is stirred rapidly, until the aqueous medium becomes acid to litmus, then filtered and air dried. An %-93% yield of N-thiotrichloromethyl amide of high purity is thus obtained. The reaction may be carried out at room temperature. In cases where the amide is readily hydrolyzed in. alkaline solution, it may be advantageous to cool the reaction mixture as low as 0 C.

The metal compound used to supply the necessary alkaline solution is a compound of an alkali metal such as lithium, sodium and potassium, and the like. Because of cost factors, sodium and potassium are preferred. The alkali is present preferably in amounts equivalent to the amide used. While other basic compounds may be used, it is desirable to use the alkali hydroxides because of the consequent avoidance of thepresence of other anion radicals which might have to be removed.

Variations on. theseprocedures can be made,

of course. Thus, the alkali metal amide salts, if available; can be dissolved directly in water and theprocess further carried on as indicatedabove for theaqueous solution reaction. Ihe amides. can also be dispersed directly in the organic.

media and finely divided alkali hydroxide or sodium added, thus forming the salt in situ. The process is thenfurther carried on as described above.

The following.- examples are given to illustratethis invention and include both the preparation of the N-thiotrichloromethyl amide compounds.

by the indicated methods, and test results obtained on the activity of these organic com-- poundscontaining the NSCC13 group.

EXAMPLE I Preparation of N-thiotrichloromethyl-5-methyl- 5-ethyloxazolz'dz'ne-2,4-dione Forty-eight grams, (0.3 mole) of 5-methyl-5- ethyloxazolidine-2,4-dione was charged to a 500 cc. Erlenmeyer flask equipped with a dropping funnel. Thirteen and one-half grams of sodium hydroxide'dissolved'in 300cc. of water was added andythemixture. stirred until solution was complete. The reaction mixture was cooled to 10 C. andwhilestirring rapidly, 62 grams (0.3 mole) ofsperchloromethyl mercaptan was added from the dropping funnel over a period of 10 minutes. The; temperature of the reaction mixture was maintained at l0-20$" C. After 1%; hours, the reaction was discontinued and the mixture filtered with suction. After air drying, 36 grams of white powder (89% yield) was recovered. The material was recrystallized from petroleum ether, giving '7 6 grams of white crystalline product having a melting point of 83-84 C. The product 68 grams (92% yield) of a, crystalline product having a melting point of 111-116 C.

Analysis Per cgent Per Igent Per gent Percgent 5 Analysis Per gent Per E([Jent Per gent Perllent PerNOent Found 29.31 3.04 11.20 36.29 Found 19.14 0.92 24.22 39.66 5.10 Theory 28. 70 2. 75 10. 95 36. 35 Theory 18.03 0. 75 24. 00 39. 91 5. 24

Th compounds described in this invention may EXAMPLE n thus be applied to parent materials to retard or PTepaTatiOn N- O e y -p e i l prevent fungus growth and mildew formation. benz ne u fo Since many of these compounds are exceptionally I e f hen 1ben nonphytctoxic, they may be applied safely to a o. or water containing 7.2 grams sodium hydroxide. P mammals to Winch be apphed While stirring rapidly at room temperature, 33.5 protefitlve P9 1 are 18am, Wood (0.18 mole) grams of perchloromethyl mercaptan 9 coated g and Substances was added dropwise from a dropping funnel over These compcilmds W, reduced an a period of minutes. After stirring for one palpable poivderanqappheq as an undlluted dust hour the solution became acid. After filtering or mlxed i sohd Carmel" such. as clay tailc the precipitate and air drying the residue, the and m as d E earners i m product was recrystallized from n-heptane. Reh In Order 'l mto covered 64 grams of a tan-colored solid having f i fi i i at (See Freafr a melting point of 106108 C. After recrystal- 5 i ff 'i of lnsemmlqes 9 5 and Herbl' lizing from methyl alcohol, 42 grams of a lighti i" f ii i g spraiy colored crystalline material was obtained havm 1 1 N 813181 s so u ing a melting point of 111.5-112.5 C. f t m j Ven as water. When applied as a spray in water, it may be desirable to incorporate wetting agents. Analysls Per Cent Per Cent Per Cent Per Cent Thecompouncls of this invention in general 9 H S 01 are soluble in organlc solvents such as acetone, 4101 2 77 18 02 27 59 ethyl alcohol, benzene, naphtha, etc., although different compounds exhibit different solubilities. Theory" 40'84 2768 The water-soluble Wetting agents that may be 35 used comprise the sulfates of long chain alcohols EXAMPLE III such as dodecanol up to octadecanol, sulfonated amide and ester derivatives, sulfonated aromatic Preparation 32 2;:g zg z and mixed alkyi-aryl suifonate derivatives, esters Zme y y a 0 n of fatty acids such as the ricinoleic ester of sorfty t grams mole) of bitol, and petroleum sulfonates of (310 to C20 dimet y y Were dissolved in 350 Of length. The non-ionic emulsifying agents such cold Water Containing 13.3 gra Sodium yas the ethylene oxide condensation products of droxide in a 1-liter Erlenmeyer flask equipped alkylated phenols may also be used. It is to be with a stirrer and dr ppin f nn Whi s irunderstood that these and similar compounds ar ring rapidly, 62 grams (0.3 mole) of perchloro- 5 intended when the term wetting agent is used methyl mercaptan was added from the dropping hereafter. funnel over a period of 10 minutes. The reac- The compounds of this invention may also be tion temperature was maintained at 15-20 C. admixed with carriers that are themselves ac- After 1.5 hours, the reaction mixture was filtered tive, such as other pafasiiicides, rmones, herbiwith suction and the residue air dried. One hunsides. fertilizers. and waiting nts. Stomach dred grams 3% yie1d) of white Solid was and contact insecticides such as the arsenates, covered The product was Soluble in acetone, fluorides, rotenone, and the various fish poisons alcohol, carbontetrachloride and benzene, but and organic insecticides, such as di-(p-chloroonly slightly soluble in heptane. phenyl) trichloroethane, benzenehexachloride, 65 and similar products may also be advantageously added. Analysis Pergent Per 1gent Per SCent Per (Sent Per 1gent EXAMPLE V Found 0125 2 33 9 32 74 19 35 Compounds oi this invention were tested for The i'jIIII 22:30 1:87 9194 33:08 15104 00 Damsltlcldal actlvlty- The values given in column I represent the percentage mortality of the test insects after 96 EXAMPLE IV hours following a two-minute immersion in a Preparation of N thiom-chlommethyl z,4 0.25% aqueous solution or suspension of the test dioxothiazolidz'ne 65 Compound- The results in column II are given as per cent 35-14 grams mole) of zil-dloxothlzPlldme mortality of the test insect after 96 hours fellowwas adder to of Water ing bloodstream injection of 0.002 cc. of a 5% grams of sodium hydroxlde. While stirring solution of the test compound p ly, 55.8 grams (0.3 ole) f P 7 The Slide Germination Technique for fungimethylmercaptan was added dropwise from a droppin funnel. The temperature reaction was not allowed to go above 35 C. The solution became acid Within 15 minutes. The product was filtered with suction and air dried.- Recovered cidal testing Was carried out as described by Wellman and McCallan (Contributions of Boyce Thompson Institute, vol. 3, No. 3, pages 171-176) and is listed in column III as concentration of test com-pound in per cent to give an LD.-50,

N-thiotrichloromethyl-N-phenyl-benzene-sulfonamide 20 Column I Column II Column III BloodstreamInsect.

Contact Insecticidal 2 32 32 5 52; Fungicidal Inhibiting Con- Compound ctlvlty ma (American centration, Per Cent Roach Blattella Omelpeltus Al I germa'm'ca socz'atus temen'a Sc erotinia (German (Milk Weed Female Male solania fructicola Roach) Bug) 7 /CHa CH\3 /O=O CH3 l /C=O I N-SOO1: O

1-acety1-3-thiotrichloromethyl-5,5-dimethylhydantoin 100 40 100 0. 001-0. 0001 0. 0010. 0001 CH H I H CH3CCHaCN NSCC1:

3-thiotrichloromethyl-S-methy1-5-isobutylhydantoin. 20 10 100 100 0.01-0.001 0. 001-0. 0001 CH CH3 H 0 I CHa(l1-CH2-CCC\ OHa CH NSCCla N-thiotrichloromethyl-54500ctyloxezolidineZA-diona. 20 80 0. 01-0. 001 0. 01-0. 001

CH; O H I CH2CCO I CH: SCClz N-thiotrichloromethyLS-methyl-5-cyc1opropy1oxazo1idine-2,4-dinne 80 0 100 100 0. 001-0. 0001 0. 001-0. 0001 IS]- I SCC1: O C4H9 N-thiotrich1oromethyl-N-buty1-benzenesulfonamide 0. 1-0. 01 0. 01-0. 001

It is to be understood that the invention is not 4. As new chemical compounds, N-thiotrilimited to the specific examples which have been chloromethyl sulfonamicles. offered merely as illustrations, since other deriva- 5. As new chemical compounds, N-thiotritives can be prepared, and that modifications chloromethylhydantoins.

may be made without departing from the spirit 6. As a new chemical compound, N-thiotriof the invention. chloromethyl-5,5-dimethyloxazolidine-2,4-dione. What is claimed is: '7. As a new chemical compound, l-acetyl- 1. As new chemical compounds, N-thiotri- 3-thiotrichloromethy1-5,5-dimethylhydantoin. chloromethyl amides. 8. As a new chemicalcompound, N-thiotri- 2. As new chemical compounds, N-thiotrichloromethyl-N-butylbenzenesulfonamide. chloromethyl oxazolidine-diones. 9. A fungicidal composition containing an 3. As new chemical compounds, N-thiotri- N-thiotrichloromethyl amide as an active inchloromethyl-ZA-dioxo-thiazolidines. gredient admixed with a surface active dispers- 11 ing agent which lowers the surface tension of water and thereby promotes aqueous colloidal dispersions of the amide.

10. A fungicidal composition comprising an N-thiotrichloromethyl amide as an active ingredient dissolved in a solvent therefor.

11. A fungicidal composition comprising an N-thiotrichloromethyl amide as an active ingredient admixed with a solid, powdered, inert diluent.

12. A fungicidal composition as in claim 11 in which the inert diluent is a clay.

13. A fungicidal composition as in claim 12 in which the clay is bentonite.

14. A fungicidal dust composition comprising 15 an N-thiotrichloromethyl-hydantoin as an active ingredient admixed with bentonite.

15. A fungicidal dust composition comprising '1-acety1-3-thiotrichloromethyl 5, 5 dimethyl- 1o agent.

ROGER S. HAWLEY. ALLEN R. KIT'ILESON. PAUL V. SMITH, JR.

No references cited. 

1. AS NEW CHEMICAL COMPOUNDS, N-THIOTRICHLOROMETHYL AMIDES. 